Modulation of AMPK by esomeprazole and canagliflozin mitigates methotrexate-induced hepatotoxicity: involvement of MAPK/JNK/ERK, JAK1/STAT3, and PI3K/Akt signaling pathways
Naunyn-Schmiedeberg s Archives of Pharmacology,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 7, 2025
Abstract
This
research
investigated
the
hepatoprotective
effects
of
esomeprazole
(ESOM)
and
canagliflozin
(CANA)
against
methotrexate-induced
liver
toxicity,
focusing
on
AMPK
modulation
its
regulation
MAPK/JNK/ERK,
JAK1/STAT3,
PI3K/Akt
pathways.
Fifty
male
Wistar
rats
were
divided
into
five
groups:
control,
MTX,
three
pretreatment
groups
receiving
ESOM
(30
mg/kg),
CANA
or
their
combination.
administered
for
8
days
before
1
day
after
a
single
MTX
injection
(20
mg/kg,
intraperitoneally)
9
to
induce
hepatotoxicity.
Liver
injury,
oxidative
stress,
inflammation,
apoptosis
assessed
using
biochemical,
histopathological,
immunohistochemical,
qRT-PCR,
western
blot
analyses.
Data
analyzed
by
one-way
analysis
variance
(ANOVA)
Tukey’s
post
hoc
test,
with
significance
at
p
<
0.05.
Results
presented
as
mean
±
standard
error
(SE).
Rats
that
received
showed
significant
damage,
marked
elevated
ALT,
AST,
MDA,
MPO,
iNOS,
TNF-α,
IL-6,
IL-1β
levels
(
0.01)
decreased
antioxidant
enzymes
(HO-1,
Nrf2,
GSH).
Immunohistochemistry
revealed
increased
NF-kB
p65
caspase-9
expression
0.01),
correlating
histopathological
changes.
Pretreatment
reduced
enzyme
levels,
improved
histology,
restored
balance,
inhibited
inflammatory
pathways
via
p38MAPK/NF-kB
JAK1/STAT3
0.01).
Moreover,
preserved
activity
prevented
caspase-dependent
Additionally,
combination
treatment
synergistic
effects,
demonstrated
improvements
in
all
measured
parameters.
These
findings
suggested
had
potential
therapeutic
agents
alleviating
MTX-induced
hepatotoxicity
warranted
further
investigation
future
research.
Язык: Английский
Regulation of pyroptosis by NF-κB signaling
Frontiers in Cell Death,
Год журнала:
2025,
Номер
3
Опубликована: Янв. 7, 2025
Pyroptosis
is
a
form
of
proinflammatory
cell
death
characterized
by
inflammasome
activation,
pore
formation,
and
the
release
pro-inflammatory
cytokines
such
as
interleukin-1β
(IL-1β)
IL-18
upon
rupture.
Nuclear
factor-κB
(NF-κB),
prototypical
transcription
factor,
plays
critical
role
in
immune
system
regulation.
Recent
research
highlights
multifaceted
roles
NF-κB
signaling
pyroptosis.
Various
immunologically
relevant
ligands
their
receptors
can
activate
pathway
to
promote
pyroptosis,
with
Toll-like
(TLRs),
IL-1
(IL-1Rs),
TNF
(TNFRs)
being
most
prominent.
regulates
key
components
inflammasomes
involved
particularly
NLRP3
inflammasome.
studies
also
indicate
that
modulates
activation
NLRC4
AIM2
through
distinct
pathways
diverse
inflammatory
conditions,
acute
lung
injury
neuroinflammation.
Additionally,
mediates
production
cytokines,
including
IL-1β,
IL-33,
TNF-α,
which
further
regulate
This
review
examines
recent
advances
understanding
regulating
pyroptosis
during
infection
inflammation.
Язык: Английский
Advances in micro- and nano- delivery systems for increasing the stability, bioavailability and bioactivity of coenzyme Q 10
Critical Reviews in Food Science and Nutrition,
Год журнала:
2025,
Номер
unknown, С. 1 - 18
Опубликована: Янв. 16, 2025
Coenzyme
Q10
acts
as
a
liposoluble
quinone
compound
in
mitochondrial
oxidative
phosphorylation,
serving
an
electron
carrier
and
protecting
the
cell
membrane
structure
antioxidant.
has
notable
health
benefits,
including
anti-aging,
anti-inflammatory,
prevention
of
cardiovascular
diseases,
assistance
cancer
treatment.
However,
its
poor
water
solubility,
unstable
chemical
properties,
low
bioavailability
significantly
limit
application.
This
article
reviewed
design
development
processes
various
delivery
systems
for
coenzyme
Q10,
discussing
advantages
disadvantages
different
their
improvement
strategies,
improvements
stability
accessibility
emulsions,
achieving
higher
penetration
rates
oleogels,
reducing
use
toxic
substances
production
process
liposomes.
The
mechanisms
behind
Q10's
were
analyzed,
bioactivity
research
prospects
also
discussed.
In
summary,
this
review
offered
valuable
insights
into
application
which
may
provide
reference
pharmaceuticals,
cosmetics,
products,
other
industries
future.
Язык: Английский
Cadmium exposure induced spleen inflammation by activating the MAPK/NF-κB/ NLRP3 signaling pathway and the intervention effect of Astilbin
Veterinary Immunology and Immunopathology,
Год журнала:
2025,
Номер
281, С. 110889 - 110889
Опубликована: Янв. 31, 2025
Язык: Английский
Melatonin augments anti-tumor activity and alleviates nephrotoxicity of gemcitabine in a pancreatic cancer xenograft model targeting P62/Keap1 pathway
Naunyn-Schmiedeberg s Archives of Pharmacology,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 18, 2025
Abstract
Although
gemcitabine
is
a
primary
chemotherapy
for
pancreatic
cancer,
its
effectiveness
limited
by
chemoresistance
and
nephrotoxicity,
posing
significant
clinical
challenges.
Therefore,
the
development
of
novel
therapeutic
approaches
to
prevent
malignancy
remains
crucial.
This
study
aimed
investigate
potential
melatonin
in
enhancing
gemcitabine’s
anticancer
efficacy
while
mitigating
nephrotoxic
effects
through
modulation
Keap1/p62
pathway.
A
cancer
xenograft
model
was
established
rats,
which
received
either
(50
mg/kg,
I.P.),
or
their
combination
three
times
per
week
2
weeks.
Our
findings
demonstrate
that
potentiates
cancer-suppressing
via
Kelch-like-ECH
associated
protein-1
(Keap1)/p62
pathway,
resulting
reduced
fibrosis,
oxidative
stress,
inflammatory
markers.
Additionally,
significantly
mitigated
gemcitabine-induced
nephrotoxicity.
These
results
suggest
may
serve
as
an
adjuvant
therapy
treatment,
reducing
adverse
effects.
Язык: Английский